PCR detection of adenovirus in a bone marrow transplant recipient: hemorrhagic cystitis as a presenting manifestation of disseminated disease

Abstract

Adenoviruses (AdV), causing fatal disseminated infections in bone marrow transplant (BMT) recipients, are associated not only with hemorrhagic cystitis (HC) but also with hepatitis, conjunctivitis, and viral interstitial pneumonia. The importance of this virus as a cause of disseminated disease, however, has remained underappreciated. AdV infection has been diagnosed primarily through the use of cell culture. The fact that cell culture is insensitive for detecting this virus has hindered recognition of the role that AdV may play in morbidity and mortality in BMT recipients. To emphasize these points, we describe a patient who presented with HC due to AdV serotype 11, genotype c, and died with disseminated infection. In addition to cell culture, this study used a newly developed PCR-based method, capable of detecting all AdV serotypes tested, including different genotypes of serotype 11. The PCR result was positive in all culture-positive samples, including samples of urine, conjunctiva, and bronchoalveolar lavage (BAL). Importantly, the PCR method provided evidence of urinary shedding of AdV in a pretransplant, culture-negative specimen and showed dissemination in a subset of culture-negative specimens, including BAL, blood, and bone marrow samples. The lack of widespread awareness of the fact that localized infections may presage dissemination, and the previous associated lack of rapid, sensitive diagnostic assays, has impaired recognition of AdV infections in patients undergoing BMT. Early detection may contribute to therapy modification and avoidance of unwarranted diagnostic procedures. It may also assist in epidemiologic control of this highly infectious pathogen and lead to a renewed interest in preventive and therapeutic approaches.

FIG. 1

Detection of AdV in samples from different body sites by the PCR-based method. Lanes: M, molecular size marker; NEG, negative control (water); POS, positive control (purified DNA from AdV serotype 2); Urine 1, urine sample obtained on day −4; Conj, conjunctival-swab sample; Oral Ves., perioral-vesicle swab; Urine 2, urine sample obtained on day 45; BAL, BAL sample obtained on day 34.

FIG. 2

Detection of AdV in blood by the PCR-based method. Plasma, serum, erythrocyte (Red Cells), and whole-blood (W. Blood) samples were obtained on day 73; bone marrow (B. Marrow) samples were obtained on day 52. The negative (Neg) control was water, and the positive (Pos) control was purified DNA from AdV serotype 2. M, molecular size marker.